RESUMEN
BACKGROUND/AIMS: The medial amygdala (MeA) responds to olfactory stimuli and alters reproductive physiology. However, the neuronal circuit that relays signals from the MeA to the reproductive axis remains poorly defined. This study aimed to test whether MeA kisspeptin (MeAKiss) neurons in male mice are sensitive to sexually relevant olfactory stimuli and transmit signals to alter reproductive physiology. We also investigated whether MeAKiss neurons have the capacity to elaborate glutamate and GABA neurotransmitters and potentially contribute to reproductive axis regulation. METHODS: Using female urine as a pheromone stimulus, MeAKiss neuronal activity was analysed and serum luteinizing hormone (LH) was measured in male mice. Next, using a chemogenetic approach, MeAKiss neurons were bi-directionally modulated to measure the effect on serum LH and evaluate the activation of the preoptic area. Lastly, using in situ hybridization, we identified the proportion of MeAKiss neurons that express markers for GABAergic (Vgat) and glutamatergic (Vglut2) neurotransmission. RESULTS: Male mice exposed to female urine showed a two-fold increase in the number of c-Fos-positive MeAKiss neurons concomitant with raised LH. Chemogenetic activation of MeAKiss neurons significantly increased LH in the absence of urine exposure, whereas inhibition of MeAKiss neurons did not alter LH. In situ hybridization revealed that MeAKiss neurons are a mixed neuronal population in which 71% express Vgat mRNA, 29% express Vglut2 mRNA, and 6% express both. CONCLUSIONS: Our results uncover, for the first time, that MeAKiss neurons process sexually relevant olfactory signals to influence reproductive hormone levels in male mice, likely through a complex interplay of neuropeptide and neurotransmitter signalling.
Asunto(s)
Amígdala del Cerebelo/fisiología , Kisspeptinas/fisiología , Hormona Luteinizante/sangre , Neuronas/fisiología , Feromonas/farmacología , Administración por Inhalación , Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/metabolismo , Animales , Clozapina/análogos & derivados , Clozapina/farmacología , Ácido Glutámico/metabolismo , Kisspeptinas/genética , Masculino , Ratones , Ratones Transgénicos , Feromonas/administración & dosificación , Feromonas/orina , Área Preóptica/fisiología , Proteína 2 de Transporte Vesicular de Glutamato/metabolismo , Proteínas del Transporte Vesicular de Aminoácidos Inhibidores/metabolismo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Outcomes of non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD n = 587) and interstitial lung disease (ILD n = 34) treated with curative-intent radiotherapy were retrospectively investigated. Presence of ILD but not decreased forced expiratory volume in 1-second correlated with poor overall survival. Increased breathlessness and oxygen requirements after radiotherapy were observed in severe/very severe COPD and ILD.